- Type 2 diabetes mellitus: offered first-line alongside metformin, or alone if metformin is unsuitable (see NICE guidance)
- Not licensed in type 1 diabetes in the UK, owing to a particularly high risk of DKA
- Heart failure
- Chronic kidney disease, slowing progression
- Reduce HbA1c by ~11mmol/mol, with modest weight loss and reduced cardiovascular mortality
SGLT2 Inhibitors
SGLT2 Inhibitors
Resources
- Non-insulin diabetes medicines: a narrative review for anaesthetists and intensivists (BJA, 2025)
- Perioperative management of patients taking sodium-glucose cotransporter 2 inhibitors: SPAQI multidisciplinary consensus statement (BJA, 2026)
- Peri-operative management of diabetes mellitus: a multidisciplinary consensus statement (Association of Anaesthetists and JBDS-IP, 2026)
- Elective peri-operative management of adults taking glucagon-like peptide-1 receptor agonists, glucose-dependent insulinotropic peptide agonists and sodium-glucose cotransporter-2 inhibitors: a multidisciplinary consensus statement (Anaesthesia, 2025)
- Risk of perioperative discontinuation of SGLT2 inhibitors (BJA, 2024)
- Update on the perioperative management of diabetes mellitus (BJA Education, 2024)
- Dose-dependent relationship between SGLT2 inhibitor hold time and risk for postoperative anion gap acidosis (BJA, 2023)
- Diabetes medication pharmacology (BJA Education, 2017)
- Sodium-glucose co-transporter 2 (SGLT2) inhibitors, or 'flozins', cause glycosuria by blocking renal glucose reabsorption
- Initially diabetes drugs, they are now foundational treatment for heart failure and chronic kidney disease, irrespective of diabetes
- Their key peri-operative concern is euglycaemic diabetic ketoacidosis (euDKA)
| Drug | Half-life | Indications |
| Canagliflozin | ~12-13hrs | T2DM, HF, CKD |
| Dapagliflozin | ~12-13hrs | T2DM, HF, CKD |
| Empagliflozin | ~12hrs | T2DM, HF, CKD |
| Ertugliflozin | ~16hrs | T2DM |
- Oral, once daily
- After ~72hrs without a dose <1% of drug remains in the circulation, although glycosuria persists for longer
- Combination products exist (e.g. dapagliflozin with metformin)
- SGLT2 is a sodium-glucose symport in the proximal convoluted tubule responsible for ~90% of renal glucose reabsorption (see renal glucose handling)
- Inhibition causes glycosuria (several grams per day) and natriuresis, lowering plasma glucose
- This is insulin-independent, so they lower glucose without causing hypoglycaemia
- Cardiorenal benefits are multifactorial and independent of glucose lowering:
- Osmotic diuresis and natriuresis reduce fluid retention, blood pressure and afterload
- Improved endothelial function and reduced arterial stiffness
- Antioxidant effects and improved mitochondrial function
Renal
- Osmotic symptoms: polyuria, dehydration, polydipsia
- Genital candidiasis and urinary tract infection
- Volume depletion and hypotension, particularly in the frail
Euglycaemic diabetic ketoacidosis
- Ketoacidosis with normal or only modestly raised glucose (usually <14mmol/L)
- Glycosuria lowers the insulin:glucagon ratio, releasing free fatty acids that are converted to ketones, mimicking starvation
- Ketone reabsorption in the proximal tubule is also increased
- The incidence of perioperative euDKA is ~0.2% for elective and ~1.1% for emergency procedures
- Diagnostic criteria (SPAQI): glucose <11.1mmol/L, β-hydroxybutyrate ≥3mmol/L, and pH ≤7.3, bicarbonate ≤18mmol/L or anion gap >10
- Risk factors:
- T2DM as very few cases occur in patients without diabetes
- Insulin use, or reduction or omission of insulin doses
- Poor glycaemic control inc. previous DKA
- Fasting, dehydration, very low carbohydrate diets (e.g. before bariatric surgery)
- Surgical stress: emergency, major and cardiac surgery
- Acute illness, infection, alcohol
- Treated as for DKA, with glucose given early as blood glucose is already low
Perioperative management
- The joint CPOC/AoA guidance is to omit on the day before and the day of surgery
- As most patients take them in the morning, this gives a 48-54hr cessation period balancing euDKA risk against worsening glycaemic control
- Stop at the start of a very low energy or liver reduction diet e.g. before bariatric surgery
- Emergency surgery: withhold on admission and monitor capillary glucose and ketones
- If the drug has not been stopped before elective surgery, postponement is probably unnecessary although make a shared decision and monitor glucose and ketones if proceeding
- Guidance varies however e.g.
- North American and European guidance is to stop 3-4 days before surgery, regardless of indication
- Antiopdean guidance is to stop either on the day of surgery (minor procedures) or three days before
- The SPAQI (2026) guidance was tailored to the indication:
- No T2DM: continue
- T2DM and another indication (heart failure, CKD): continue
- T2DM alone and cardiac surgery: stop 3 days before
- Minimise fasting from carbohydrates
- If continued for major surgery, consider monitoring for euDKA in procedures >3hrs:
- A normal anion gap virtually excludes euDKA
- An anion gap >10 should prompt measurement of blood β-hydroxybutyrate and pH
- Consider prophylactic dextrose ± insulin infusion in high-risk patients, e.g. T2DM continuing an SGLT2 inhibitor for cardiac surgery
- Blood ketones are preferred to urine ketones, as urinary tests detect acetoacetate and may delay diagnosis
- Measure capillary ketones daily until eating and drinking normally, even if blood glucose is normal
- Restart once eating and drinking normally, ketones are normal and the patient is clinically stable
- Discontinue in critical illness with frequent assessment of ketones
- Do not restart after bariatric surgery until discussed with the prescriber, as patients remain on reduced carbohydrate diets
- Educate patients on euDKA symptoms (nausea, vomiting, abdominal pain, malaise) and sick day rules